Kaposi sarcoma is a multicentric angioproliferative neoplasm of lymphatic endothelium-derived cells. Although this malignancy is relatively frequent after solid-organ transplant, it is extremely rare after bone marrow transplantation. Allogeneic stem cell trans-plantation is associated with severe prolonged immunosuppression; however, a few cases of Kaposi sarcoma after hematopoietic stem cell transplant were previously reported. Here, we report a case of Kaposi sarcoma after haploidentical allogeneic hematopoietic stem cell transplant. The patient was a known case of acute myelogenous leukemia and underwent trans-plant after relapse. Four months posttransplant, she presented with 3 dark blue or purplish small nodules on her face above the upper lip. Histopathologic study confirmed Kaposi sarcoma. Serum antibody against human herpes virus type 8 was positive. After discontinuation of immunosuppressive medication and cryotherapy for local control, Kaposi sarcoma skin nodules healed with residual pigmented skin lesions. The patient is currently in complete remission for Kaposi sarcoma and cured from acute myelogenous leukemia 36 months after stem cell transplant. Only 14 cases of Kaposi sarcoma after hematopoietic cell transplant have been previously reported in the literature (11 after allogeneic and 3 after autologous hematopoietic stem cell transplant). According to our knowledge from literature review, this case is the first report of Kaposi sarcoma after a haploidentical HLA match transplant.
Key words : Acute myelogenous leukemia, HLA haploidentical match
Hematopoietic stem cell transplant (HSCT) is an established treatment for many acquired and congenital disorders of the hematopoietic system. Kaposi sarcoma was first described in 1872 by Kaposi as a progressive sarcoma.1 It is a multicentric angio-proliferative neoplasm of lymphatic endothelium-derived cells. Kaposi sarcoma is classified into 4 types based on the clinical condition in which it develops: (1) sporadic or classic subtype, (2) endemic, (3) AIDS associated or epidemic Kaposi sarcoma, and (4) iatrogenic subtype in patients treated with immunosuppressive therapy medications, particularly in organ transplant recipients (typically seen with renal allografts).
Kaposi sarcoma, which is shown relatively frequently after solid-organ transplant, is extremely rare after bone marrow transplant. Allogeneic stem cell transplant is associated with severe prolonged immunosuppression; however, a few cases of Kaposi sarcoma after HSCT were previously reported.2-10 The cause of Kaposi sarcoma is complex but is almost certainly dependent on a gamma herpes virus, human herpes virus type 8 (HHV-8), as causal agent.11,12 After allogeneic stem cell transplant, Kaposi sarcoma can develop when a patient is positive for HHV-8.
Here, we report a case of Kaposi sarcoma after haploidentical allogeneic HSCT. The patient was a known case of acute myelogenous leukemia (AML) and underwent transplant after relapse. According to our knowledge from literature review, this case is the first to report Kaposi sarcoma after haploidentical HLA-matched transplant.
A 44-year-old female patient was diagnosed with AML and was treated 2 times with standard regimen of 7+3 with cytarabine and anthracycline. Because she did not respond, we treated her with a salvage regimen of fludarabine-cytarabine-idarubicin (FLAG-IDA), which induced complete remission. Immediately after diagnosis, we attempted to locate an HLA identical sibling or family member, but no suitable matched donor was found. The patient’s disease relapsed 3 months later, and she received reinduction with fludarabine-cytarabine-mitoxantrone and again achieved remission. We decided to do an HLA haploidentical transplant for this high-risk patient. Written informed consent was obtained from the patient.
Her sister, the donor, was HLA haploidentical. Both the patient and the donor were seronegative for hepatitis B, hepatitis C, human immunodeficiency virus, and Epstein-Barr virus before transplant. The conditioning chemotherapy regimen was busulfan-based myeloablative conditioning, which included 14 mg/kg busulfan for 4 days, 120 mg/kg cyclophosphamide for 3 days, and 2.5 mg/kg antithymocyte globulin for 4 days. Prophylaxis of graft-versus-host disease consisted of cyclosporine A, short-term methotrexate, and mycophenolate mofetil. The patient received 5.2 × 108/kg of body weight unmanipulated peripheral blood mononuclear cells (5.8 × 106/kg CD34-positive cells). The patient was treated in a high-efficiency particulate air-filtered room and remained in the isolated room until engraftment. Prophylactic antibiotics, antifungals, and antivirals (acyclovir) were administered during the neutropenic period. All blood products, including packed cells and platelets, were irradiated with gamma rays to prevent posttransfusion graft-versus-host disease.
Granulocyte engraftment (absolute neutrophil count > 500/mm3 for 2 consecutive days) was achieved by postoperative day 12, and platelet engraftment (platelet count > 20,000/mL without transfusion for 2 consecutive days) was achieved on postoperative day 16. On postoperative day 17, the patient developed symptoms of grade 1 skin graft-versus-host disease. Over the next few months, we reduced the immunosuppressive treatment gradually, and our plan was tapered over 6 months. Four months after transplant, she presented with 3 dark blue or purplish small nodules on her face above the upper lip. Histopathologic study confirmed Kaposi sarcoma. Serum antibody against HHV-8 was positive. We immediately discontinued cyclosporine. Computed tomography examination of chest and abdomen did not show any visceral or nodal involvement. After discontinuation of immunosuppressive medication and cryotherapy for local control, Kaposi sarcoma skin nodules healed with residual pigmented skin lesions. The patient is currently in complete remission for Kaposi sarcoma and cured from AML without signs of chronic graft-versus-host disease after 36 months from stem cell transplant.
In this case report, we present an Iranian patient with Kaposi sarcoma of the skin associated with HHV-8 appearing shortly after haploidentical allogeneic stem cell transplant. The patient was a known case of high-risk AML who received HLA haploidentical sibling HSCT with an antithymocyte globulin-containing regimen after relapse. Although it is more common in solid-organ transplant, there are only a few reports of Kaposi sarcoma after hematopoietic cell transplant. The neoplasm arose 4 months after HSCT during tapering of immunosuppression; therefore, prolonged immunosuppression was not the main factor in our case. In this case, intensity of immunosuppressive therapy for haploidentical transplant may be the major cause. In our center, we have long-term experience with allogeneic and autologous transplant procedures for patients with malignant and nonmalignant hematologic disorders, with more than 1400 transplants for leukemia (AML, acute lymphocytic leukemia, chronic myeloid leukemia), thalassemia, aplastic anemia, Fanconi anemia, and other congenital diseases during the past 24 years.13,14 However, this is the only experience with Kaposi sarcoma after HSCT transplant at our center, and this is the first case reported from Iran after HSCT transplant, which confirms again it is rare complication in HSCT.
Only 14 cases of Kaposi sarcoma after hematopoietic cell transplant have so far been reported in the literature: 11 after allogeneic and 3 after autologous hematopoietic cell transplant.2-10 The disease was lethal in 3 of 11 allogeneic and 1 of 3 autologous hematopoietic cell transplant patients. In adults, skin lesions were the dominant clinical manifestation.2-10 All 3 pediatric cases had visceral organ involvement, resulting in 2 fatalities (after either allogeneic or autologous HCT). Two patients (1 adult and 1 child) with autologous HCT had visceral organ involvement. The adult patient, while in complete remission for his hematological malignancy, died from wide-spread Kaposi sarcoma. The pediatric case responded to recombinant alpha-interferon and survived.10
Our case did not have visceral involvement and responded to discontinuation of immunosuppressive therapy and local treatment without need for systemic chemotherapy. Presence of HHV-8 serology before transplant was not known in this case and not a routine examination in our center.
According to previous reports, if immune recovery is expected and the disease is limited to the skin, a watch and wait strategy can be more useful than intensive chemotherapy. Our case also showed recovery after discontinuation of immunosup-pressive therapy and some local therapy.
In conclusion, although Kaposi sarcoma is a rare complication of HSCT, it should be considered in patients after stem cell transplant, especially in recipients of haploidentical HLA-matched allogeneic transplant patients who have more intensive immunosuppressive therapy.
DOI : 10.6002/ect.2017.0075
From the Hematology Research Center, Department of Hematology, Medical Oncology
and Stem Cell Transplantation; Shiraz University of Medical Sciences, Shiraz,
Acknowledgements: The authors have no sources of funding for this study and have no conflicts of interest to declare.
Corresponding author: Mani Ramzi, Professor of Hematology and Medical Oncology, Department of Hematology, Medical Oncology, and Stem Cell Transplantation, Shiraz University of Medical Sciences, Shiraz, Iran
Phone: +98 711 36474301